Plasma membranes from rat pancreas will be radiolabeled by 14C-ADP-ribosylation with cholera toxin, then solubilized, and the radiolabeled species will be isolated by HPLC. Recombination studies of this material, with the solubilized adenylate cyclase subunit from brain synaptosomal membranes pretreated with GIP-Sepharose, will be conducted in the presence of liposomes. Kinetic parameters of pancreatic calmodulin-stimulated cyclic GMP phosphodiesterase (isolated on calmodulin-sepharose) and of the soluble and particulate guanylate cyclases will be examined. Binding protein(s) for cyclic GMP will be tested before and after pancreozymin (CCK) stimulation of intact acinar Muscarinic receptors will be tested in rat pancreatic plasma membranes in the absence and presence of guanyl nucleotides. The degradation of CCK-8 by aminopeptidase(s) and proteases in pancreatic plasma membranes and brain synaptosomes will be compared by HPLC. The biosynthesis of CCK-8 will be examind in vivo in gut. The sulfotransferase activity allowing the sulfatation of the tyrosine residue in CCK-8 will be tested in gut and brain. Specific receptors for VIP will be further compared in pancreas, liver, and heart. The turnover of these receptors will be tested, after isoproterenol treatment, in heart and liver. The kinetic and thermodynamic parameters of adenylate cyclase activation by VIP and secretin will be examined in the three organs.